J Menopausal Med.  2014 Apr;20(1):14-20.

Hereditary Risk Evaluation for Borderline Ovarian Tumors Based on Immunohistochemistry

• Park JM
• Kim MK

Abstract

OBJECTIVES
Borderline ovarian tumors (BOT) are premalignant lesions. Approximately 10% of all epithelial ovarian cancers are known to be hereditary with hereditary breast and ovarian cancer (HBOC) accounting for approximately 90% of cases; the remaining 10% are attributable to Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). The aim of our study is to estimate this risk based on screening immunohistochemistry (IHC).
METHODS
Thirty-four patients diagnosed with BOT were identified. Family history, clinical characteristics, and IHC data (breast cancer 1, early onset [BRCA1], breast cancer 2, early onset [BRCA2], mutS homolog 2 [MSH2], mutL homolog 1 [MLH1]) were collected for all cases from the patients' medical charts. Nuclear staining of the tumor was scored as negative and positive.
RESULTS
Among 32 patients, 14 (44%) had serous type and 18 (56%) had mucinous type. The mean patient age was 44 years (range 19-86).The number of patients with weak IHC staining for MSH2 and BRCA2 was 1 (3%) and 6 (19%) respectively. The median follow up was 21.8 months.
CONCLUSION
According to the results, we discovered that 3% and 19% of patients with BOT had a risk of hereditary cancer based on IHC analysis respectively. This pilot study may help clinician to counsel effectively for confirmative tests.

Keyword

Lynch syndrome; Ovarian neoplasmsms

MeSH Terms

Breast
Breast Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis
Follow-Up Studies
Humans
Immunohistochemistry*
Mass Screening
Mucins
Ovarian Neoplasms
Pilot Projects
Mucins

Figure

• 

  Fig. 1 Immunohistochemical staining of BRCA1, BRCA2, and MSH2. (BRCA1: breast cancer 1, early onset, BRCA2: breast cancer 2, early onset, MSH2: mutS homolog 2)

Reference

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61:69–90.

2. Swanton A, Bankhead CR, Kehoe S. Pregnancy rates after conservative treatment for borderline ovarian tumours: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2007; 135:3–7.

3. Gershenson DM. Clinical management potential tumours of low malignancy. Best Pract Res Clin Obstet Gynaecol. 2002; 16:513–527.

4. Lalwani N, Shanbhogue AK, Vikram R, Nagar A, Jagirdar J, Prasad SR. Current update on borderline ovarian neoplasms. AJR Am J Roentgenol. 2010; 194:330–336.

5. Silva EG, Gershenson DM, Malpica A, Deavers M. The recurrence and the overall survival rates of ovarian serous borderline neoplasms with noninvasive implants is time dependent. Am J Surg Pathol. 2006; 30:1367–1371.

6. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001; 68:700–710.

7. Narod SA, Boyd J. Current understanding of the epidemiology and clinical implications of BRCA1 and BRCA2 mutations for ovarian cancer. Curr Opin Obstet Gynecol. 2002; 14:19–26.

8. Whittemore AS, Gong G, Itnyre J. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three US population-based case-control studies of ovarian cancer. Am J Hum Genet. 1997; 60:496–504.

9. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994; 266:66–71.

10. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995; 378:789–792.

11. Aarnio M, Sankila R, Pukkala E, Salovaara R, Aaltonen LA, de la Chapelle A, et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999; 81:214–218.

12. Heo EJ, Park JM, Lee EH, Lee HW, Kim MK. A case of perimenopausal endometrial cancer in a woman with MSH2 germline mutation. J Menopausal Med. 2013; 19:143–146.

13. Burgart LJ. Testing for defective DNA mismatch repair in colorectal carcinoma: a practical guide. Arch Pathol Lab Med. 2005; 129:1385–1389.

14. Boyd J, Luo B, Peri S, Wirchansky B, Hughes L, Forsythe C, et al. Whole exome sequence analysis of serous borderline tumors of the ovary. Gynecol Oncol. 2013; 130:560–564.

15. Varga J, Bilecová-Rabajdová M, Ostró A. Borderline ovarian tumor - a case report with genetic testing. Eur J Gynaecol Oncol. 2013; 34:189–192.

16. Jung KW, Park S, Won YJ, Kong HJ, Lee JY, Seo HG, et al. Prediction of cancer incidence and mortality in Korea, 2012. Cancer Res Treat. 2012; 44:25–31.

17. Dehari R, Kurman RJ, Logani S, Shih Ie M. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis. Am J Surg Pathol. 2007; 31:1007–1012.

18. McCluggage WG. The pathology of and controversial aspects of ovarian borderline tumours. Curr Opin Oncol. 2010; 22:462–472.

19. Webb PM, Purdie DM, Grover S, Jordan S, Dick ML, Green AC. Symptoms and diagnosis of borderline, early and advanced epithelial ovarian cancer. Gynecol Oncol. 2004; 92:232–239.

20. Shin JY, Kim SY, Lee KS, Lee SI, Ko Y, Choi YS, et al. Costs during the first five years following cancer diagnosis in Korea. Asian Pac J Cancer Prev. 2012; 13:3767–3772.

21. Seidman JD, Kurman RJ. Ovarian serous borderline tumors: a critical review of the literature with emphasis on prognostic indicators. Hum Pathol. 2000; 31:539–557.

22. Zanetta G, Rota S, Lissoni A, Meni A, Brancatelli G, Buda A. Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors. Gynecol Oncol. 2001; 81:63–66.

23. Prat J, Ribé A, Gallardo A. Hereditary ovarian cancer. Hum Pathol. 2005; 36:861–870.

24. Stratton JF, Gayther SA, Russell P, Dearden J, Gore M, Blake P, et al. Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med. 1997; 336:1125–1130.

25. Watson P, Butzow R, Lynch HT, Mecklin JP, Jarvinen HJ, Vasen HF, et al. The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol. 2001; 82:223–228.

26. Garg K, Levine DA, Olvera N, Dao F, Bisogna M, Secord AA, et al. BRCA1 immunohistochemistry in a molecularly characterized cohort of ovarian high-grade serous carcinomas. Am J Surg Pathol. 2013; 37:138–146.

27. Kim MK, Song SY, Do IG, Kim SH, Choi CH, Kim TJ, et al. Synchronous gynecologic malignancy and preliminary results of Lynch syndrome. J Gynecol Oncol. 2011; 22:233–238.

28. Cohen SA. Current Lynch syndrome tumor screening practices: a survey of genetic counselors. J Genet Couns. 2014; 23:38–47.

29. Jones S, Wang TL, Kurman RJ, Nakayama K, Velculescu VE, Vogelstein B, et al. Low-grade serous carcinomas of the ovary contain very few point mutations. J Pathol. 2012; 226:413–420.

30. Lee WS, Park ES, Kim DH, Kim TH, Lee HH, Chung SH. Expression of p53, p27 and Jab1 protein in epithelial ovarian tumors. Eur J Gynaecol Oncol. 2012; 33:358–362.

31. Mun MJ, Kim JH, Kim TH, Hwang JY, Jang WC. Associations between estrogen receptor gene polymorphisms and endometriosis. J Korean Soc Menopause. 2013; 19:64–73.